A 73-year-old man with diabetes presented with upper-abdominal pain and nausea. He also had a history of hypertension, a pace-maker
implant, and peripheral arterial disease treated with amputation of his left leg. His therapy included ticlopidine, enalapril,
omeprazole, and 2 mg glibenclamide/30 mg phenformin b.i.d. The patient was alert and cognitively intact. Blood pressure and
heart rate were 120/70 mmHg and 70 bpm, respectively. Radiographs of the chest and abdomen and an abdominal ultrasound study
were normal. Laboratory tests disclosed a severe lactic acidosis (pH 6.8, pCO2 14.1 mmHg, pO2 108 mmHg, HCO3 4.9 mmol/l, lactate 21 mmol/l, and anion gap 31 mmol/l). After phenformin discontinuation, the patient’s conditions rapidly
improved. He was treated with intravenous insulin and glucose (1) and discharged 7 days later in good condition.

This report confirms that phenformin-induced lactic acidosis (PLA) is still a public health problem (1,2). To our knowledge, phenformin is still used in Italy, China, and Brazil. In a Medline search, we found 12 cases that occurred
in Italy between 1981 and 1998 (2). In two patients phenformin was even brought back into use soon after, thereby questioning the belief that PLA is adequately
recognized (2). More importantly, according to data by Intercontinental Marketing Services (www.imshealth.com), 838,000 preparations of phenformin and a sulfonylurea have been sold in Italy between January and October 2005. Because
PLA occurs in 1 of 4,000 patients (3) with a mortality rate of ∼50%, these data raise worrying health care considerations. In fact, diabetic patients often have
comorbid conditions known to favor PLA.

Phenformin was removed from the U.S. market in 1977, but, surprisingly, cases of patients who have been prescribed the drug
abroad are continuously reported (1). Phenformin can also be illegally obtained online or through mail orders to replace metformin, which is more costly. Furthermore,
herbal medicines containing phenformin are also consumed in developed countries. In February 2000, the Food and Drug Administration
recalled five Chinese herbal medications containing phenformin (4), while Health Canada is currently warning consumers not to take “Shortclean,” a phenformin-based Chinese “natural” medicine
(5).

Phenformin can always be replaced by metformin, which should not be associated with a higher risk of lactic acidosis compared
with nonbiguanide therapies (6). Despite most clinicians being aware of PLA, the only way for preventing further cases is to forbid phenformin in countries
where it is still used.

Acknowledgments

Footnotes

Editor’s note: The authors had the following statement in their letter to me, with which I agree, “Most physicians are aware
of the risk of lactic acidosis in patients taking phenformin. However, this side effect is continuously observed because phenformin
is still used in Italy, Brazil, and China. We believe that the publication of our observation in an important journal like Diabetes Care may help to prompt governments of these countries to ban phenformin, just like in the rest of the world. This is the only
way to prevent further cases of this avoidable, unacceptable and life-threatening complication.”